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Abstract

The aging of the population is a universal phenomenon with direct consequences
upon the public health system. One of the main repercussions of the growth in
this sector of the population is the increased prevalence of disorders such as
dementia and depression which are very frequent among the elderly. The
relationship between cardiovascular risk factors, dementia and depression have
been addressed in many recent investigations.

Objectives

To evaluate the relationship of cognitive performance and depressive symptoms
with cardiovascular risk in the elderly.

Methods

94 high cardiovascular risk elderly patients and 160 healthy community
elderly were evaluated cross-sectionally. The Mini Mental State Examination
(MMSE) and the Geriatric Depression Scale (GDS-15) were used as the main
measures. The cutoff for presence of depression was 6 on the GDS.

Results

The high cardiovascular risk elderly group showed significantly lower scores
on the MMSE (p<0.001) and was significantly associated to depression
(p<0.001), independently of education. The logistic regression analysis
for depression as the dependent variable, age and group (healthy community
or high cardiovascular risk elderly) were kept in the final equation. Higher
age (Odds Ratio=0.92; 95% CI 0.86–0.98) and high cardiovascular risk elderly
(OR=2.99; 95% CI 1.36–6.59) were associated to depression.

Conclusions

The present findings corroborate the different cognitive performance of
elderly with high cardiovascular risk factors and the association of
depressive symptoms with this group.

Conclusões

The aging of the population is a universal phenomenon with direct consequences upon the
public health system. As life expectancy increases, the number of demented patients
worldwide is projected to grow from 24.3 million in 2001 to 81.1 million by
2040.1 Approximately 6 million
Americans and 2 million Brazilians have Alzheimer’s disease.2,3 AD is the 3rd
most expensive disease in USA, after heart disease and cancer, and is among the 10
leading causes of death among people >65 years’ old in developed countries.2 Therefore, the identification of
individuals at risk for developing dementia is essential. Early diagnosis allows
therapeutic interventions, decreases families’ level of stress, reduces incidental risk,
increases autonomy and maybe in some cases prevents or retards dementia onset.4

Since depression and dementia are among the most common mental health problems in the
elderly population, it is common to observe their comorbid presentation, which impacts
quality of life, functional decline, increase in the use of health services, increase of
morbidity and mortality.5 Depression is
probably the most frequent cause of emotional distress and worsening of life quality
among the elderly.6,7 This population is more prone to developing depression
due to reduced social perspectives, health impo­v­erish­ment, frequent losses,
biological, vascular, structural and functional changes, besides neuroendocrine and
neurochemistry dysfunction in the brain during aging.8 Therefore, development of elderly depression is multi-factorial
in nature.5 The association between
depression and dementia is also significant. Depressed elderly may present cognitive
decline, besides an increased risk for progression to dementia.9

Over the last 3 decades, a decline of cardiovascular-related mortality has been observed
in developed countries, while relatively fast and substantial increases have occurred in
developing regions, such as Brazil. According to the World Health Organization, the
tendency for increase among developing areas may persist, worsening the scenario of
already high morbidity and mortality.10 The higher risk for developing dementia is found among patients
with conditions associated to increased cholesterol levels, such as cardiovascular
diseases and atherosclerosis.11

Studies have been carried out seeking to better understand the role of atherosclerotic
disease, dyslipidemia and hypertension, predictive factors of cardiovascular risk, in
the development of cognitive deficit. The strong association between atherosclerosis and
dementia, especially Alzheimer’s disease, has previously been demonstrated. Patients
with vascular disease have shown three-fold higher risk for developing
dementia.12 Prospective
studies have shown the relationship of atherosclerotic disease and cognitive decline
among the elderly. It is presumed that atherosclerosis may cause neuronal damage through
ischemic lesions, followed by inflammatory response that leads to neuronal degeneration.
Another hypothesis is neuronal damage caused by hypoperfusion due to decreased blood
flow in the brain.13 A higher
frequency of brain ischemic events was found in dementia patients compared to
non-demented individuals. In these patients, the observation of atherosclerotic plaques
in major vessels presented strong correlation with deposition of neuritic plaques, whose
main component is the B-amyloid protein associated to Alzheimer’s disease.14 However, no association between
generalized atherosclerosis and depression in the elderly was observed.13

The link between dyslipidemia and the occurrence of cognitive deficit has been previously
evaluated. The role of higher levels of cholesterol was significant as a risk factor for
dementia in middle-age patients, but not among elderly patients.12 The substantially lower risk of
cognitive decline was demonstrated in patients over the age of 50 with the use of
statins15. Adult hypertension
increases the risk of dementia, especially when associated to
hypercholesterolemia.16

Hypertension is associated to increased risk of dementia, and control with
anti-hypertensives, mainly with angiotensin converting enzyme inhibitors, has
demonstrated a significant reduction in the incidence of dementia.12 Diabetes is an independent predictor
of risk of cognitive decline, and the metabolic syndrome, an important cardiovascular
risk factor, plays a role as a predictor of risk for dementia.17

The association of depression to cardiovascular disease is based on convincing evidence.
A bidirectional pathway was proposed for these diseases because depression is an
independent risk factor for cardiovascular events, and is more prevalent in patients
with these conditions. Depression aggravates vascular disease and is associated to
poorer outcomes.18 The association
between risk for cardiovascular events, and cognitive decline and depressive symptoms
make screening in this population imperative.

The present study aimed to evaluate the relationship of cognitive performance and
depressive symptoms with cardiovascular risk in the elderly. The performance on the Mini
Mental State Examination and the Geriatric Depression Scale among a sample of
dyslipidemic elderly outpatients with high cardiovascular risk and a sample of healthy
community elderly was compared.

Methods

A cross-sectional study was carried out for the objectives under investigation. The
sample was composed of 94 elderly recruited from the reference center for
dyslipidemia and high cardiovascular risk (Centro de Dislipidemia e Alto Risco
Cardiovascular) from Hospital de Clínicas de Porto Alegre along with 160
healthy community elderly drawn from a cohort within the catchment area of the same
hospital. All participants were aged 60 years or more. Illiteracy was not an
exclusion criterion for either of the groups.

All patients evaluated at the reference center for dyslipidemia and high
cardiovascular risk underwent a detailed clinical examination with an emphasis on
past or recent cardiovascular events, physical and neurological examination and
laboratory tests. Total cholesterol, HDL cholesterol, LDL cholesterol,
triglycerides, glucose, ALT, AST, GGTP, electrolytes, creatinine, uric acid and TSH
were the blood tests evaluated.

The inclusion criteria for dyslipidemia among the high cardiovascular risk group were
based on the clinical guidelines for treatment with statins for this disease
developed by the Brazilian Health Ministry.19 One of the three following criteria (a, b or c) had to be
met for inclusion:

cholesterol LDL>160mg/dl plus one of the following situations:
Framingham score (≥6 for men and =10 for women); age ≥55
years; hypertension; HDL <40 mg/dl; cigarette smoking.

Patients with abnormal neurological examination or previous history of stroke and
dementia were excluded from this group. All selected patients were using statins
regularly.

The group of healthy community elderly was drawn from an ongoing cohort
study.20 All selected
participants fulfilled criteria for the healthy aging study and consented to
participate. The inclusion and exclusion criteria are depicted in Table 1. Briefly, participants underwent a
standardized neuropsychological and neurological evaluation. A collateral informant
was also used to verify the history. Subjects were excluded if they had age-related
diseases or risk factors for cognitive impairment at baseline. All participants and
their collateral informants had to report normal functioning in the community at
study entry and were screened with the Clinical Dementia Rating scale.21,22 Participants with a CDR of 0.5 (suggestive of incipient
dementia) or greater (suggestive of dementia) were excluded from the sample.

Demographic data, the Mini-Mental State Examination23-25 and the
Geriatric Depression Scale (GDS-15)26 were assessed in both groups. Subjects were further categorized
into those with or without depressive symptoms according to the cutoff of 6 on the
GDS29

The study was approved by the Ethics Committee for Research of the Hospital de
Clínicas de Porto Alegre. All subjects signed an informed consent.

Data analysis

The statistical analysis was performed by the Statistical Package for the
Social Sciences (SPSS for Windows 13.0) software. Parametric
variables were analyzed with Student’s t test. The Chi-square test (with Yates
correction or Fisher exact) was used for the association analysis. One-way ANOVA
with covariance analysis and the logistic regression model were used as
multivariate models.

Results

Comparison of demographic, MMSE score and presence or absence of depressive symptoms
by GDS between the dyslipidemic patients with high cardiovascular risk and the
community healthy elderly groups are displayed in Table 2. Education was significantly higher in the healthy community
elderly group (p<0.001). The dyslipidemia with high cardiovascular risk elderly
group showed significantly lower scores on the MMSE (p<0.001) and was
significantly associated to depressive symptoms (p<0.001). On one-way ANOVA with
covariance, group (p<0.001) and educational level (p<0.001) showed independent
and significant effects on MMSE scores.

Demographic and clinical data of high cardiovascular risk group and healthy
community elderly group.

In the multivariate analysis (logistic regression) with depression as the dependent
variable, age and group (healthy community or dyslipidemia with high cardiovascular
risk elderly) were kept in the final equation (Table
3). Higher age (Odds Ratio=0.92; 95% CI 0.86–0.98) and dyslipidemia among
the high cardiovascular risk elderly group (OR=2.99; 95% CI 1.36–6.59) were
associated to depression.

Logistic regression for depression outcome with age, group (healthy elderly
or high cardiovascular risk elderly with dyslipidemia), education, MMSE and
sex as independent variables.

Discussion

This study was carried out to analyze both cognitive performance measured by the Mini
Mental State Examination (MMSE), and depressive symptoms using the Geriatric
Depression scale (GDS) in high cardiovascular risk elderly with dyslipidemia and to
compare results with healthy community elderly. We observed lower MMSE scores among
the dyslipidemia with high cardiovascular risk elderly as well as greater depression
in this group, independently of educational level. Vascular risk factors may impair
cognitive functions and are related to the occurrence of not only vascular dementia
but also Alzheimer’s disease.12
The level of evidence for these associations is highest for hypertension and
diabetes mellitus(DM), especially when these factors are assessed in middle
age.17,27-29 However,
the essential pathophysiological mechanisms were still not linked to clinical
relevance.12 Several
studies have highlighted the possible protective effect of antihypertensive therapy
on cognition while some trials are assessing the effects of statins and treatments
for insulin-resistance.15,30-33

In the logistic regression for depression controlled for education, both higher age
and high cardiovascular risk elderly were risk factors. Elderly with dyslipidemia
with high cardiovascular risk presented twice the risk of presenting depressive
symptoms than healthy community elderly from the same age group.

Emerging evidence has suggested a causal relationship between atherosclerosis and
both cognitive decline and depression in old age.34,35 In
addition, neuropathologic findings indicate that subjects with cognitive impairment
more often have vascular pathology36,37, whereas
late-life depression has been associated with white matter hyperintensity on brain
neuroimaging, assumed to be vascular in origin.18,38,39 Recognition of the relationship between
cerebrovascular disease and depressive symptoms has led to the proposition of the
term “vascular depression” to describe a clinical subtype of major depression
characterized by apathy, psychomotor changes, and cognitive impairment in the
presence of cerebrovascular disease demonstrated on neuroimaging or by focal
neurological findings (e.g., mild hemiplegia, facial droop).9,40

Considering that cognitive decline, dementia and depressive symptoms are a worldwide
problem, establishing preventive or curative treatment when available is a major
health challenge, and vascular risk factors are a promising research pathway for
these conditions.

26. Almeida OP, Almeida SA. Short versions of the geriatric depression scale: a study of
their validity for the diagnosis of a major depressive episode according to
ICD-10 and DSM-IV. Int J Geriatr Psychiatry. 1999;14:858–865.[PubMed]

37. Neuropathology Group of the Medical Research Council Cognitive
Function and Ageing Study Pathological correlates of late-onset dementia in a multicentre,
community-based population in England and Wales. Lancet. 2001;357:169–175.[PubMed]